Ramadan fasting is one of the five pillars of Islam and is compulsory for all adult Muslims who have no medical or religious excuses. Ramadan fasting is defined as a complete abstinence from food, drink, medications, sexual activity, and smoking from dawn to dusk. Regarding the kind Islamic religion, patients have permission not to fast according to the medical advice. However, most Muslim patients express their desire to fast during Ramadan month and they are very broken when their physicians inform them not to fast. There are a lot of controversies regarding Ramadan fasting for chronic kidney diseases (CKD) and hemodialysis patients with absence of strict guidelines that help nephrologists in this issue. Renal transplant recipients who have stable kidney function for at least 1 year post-transplantation can fast with cautious follow-up. Risk of dehydration due to fasting for long periods especially in the summer season is the main concern for patients with kidney stone diseases. There is still no strong evidence if that Ramadan fasting can induce renal stone formation in susceptible patients or not. However, most studies have shown that fasting for this kind of patients with good hydration after breaking the fast may be allowed without significant risk of renal colic incidence. According to the last published guidelines by the International Diabetes Federation and Diabetes and Ramadan International Alliance, Chronic dialysis or CKD stages 4 and 5 and CKD stage 3 patients are considered to be at very high risk and high risk categories, respectively, and are exempted from fasting.

Ramadan is a great spiritual month for all Muslims all over the globe. Ramadan is the ninth lunar month (29–30 day) of the Islamic calendar; so its duration varies in different seasons from year to year. Nephrologists every year are asked by their patients whether they can observe fasting during Ramadan or not. Unfortunately, there is no strong evident answer for this repeated question and all advices given to patients are largely based on individual basis and nephrologist experiences due to lack of large cohorts in this topic. The aim of this manuscript is to review the most recent studies regarding the effect of Ramadan fasting on patients with chronic kidney diseases (CKD), hemodialysis (HD), renal transplantation (RT), kidney stone diseases, and diabetic kidney disease.

Dehydration is the main issue due to complete fluid and food restriction [1]. In healthy persons, the body responds by decreasing the output of urine and increasing urine concentration without any injurious effect on kidney function as water balance is preserved by thirst and urinary concentration mechanisms. Urinary concentration is regulated by the secretion of antidiuretic hormone, while thirst favors water intake. Both mechanisms are controlled by alterations in serum osmolality and body fluid volumes [1],[2]. Ramadan fasting can affect body homeostasis and metabolism in patients with different renal diseases especially when it happens during summer with long daytime duration.

The effect of Ramadan fasting on chronic kidney diseases and hemodialysis patients

Generally, advanced CKD and HD patients are advised not to fast during Ramadan because they carry a higher risk for dehydration during long fasting hours, and are at risk for fluid overload due to increased fluid intake when breaking fast after sunset [3]. In a study, Bakhit et al.[4] have investigated 65 patients with stage 3 or higher CKD [glomerular filtration rate (GFR) <60 ml/min], with a mean age of 53 years old who fasted for15 h/day in Riyadh in the summer of 2015. Clinical and biochemical data were collected within the 3 months before fasting initiation, after fasting for at least 10 days, and 3 months after Ramadan. The authors concluded that Ramadan fasting during the summer months was associated with worsening of renal function. Clinicians need to warn CKD patients against Ramadan fasting. Mbarki et al.[5] reported high rate of acute renal failure (11.7%) in 60 CKD patients with creatinine clearance more than 15 ml/min/1.73 m2. The safety of Ramadan fasting could not be addressed in view of the small number of patients but caution should be very high in CKD patients with more intense monitoring during fasting.

NasrAllah and Osman [6] divided 131 CKD patients with stable kidney function into two groups: fasting and nonfasting [mean baseline estimated glomerular filtration rate (eGFR) was 27.7, SD 13 and 21.5, SD 11.8 ml/min/1.73 m2, respectively]. Serum creatinine was recorded at the beginning of the month, after 1 week of fasting, at the end of the month, and 3 months later. Patients were followed up for major adverse cardiovascular events. A rise of serum creatinine was noted during fasting in 60.4% of patients by day 7 and was associated with intake of renin angiotensin aldosterone system antagonists (relative risk: 2, P=0.002). They found a high rate of major adverse cardiovascular event among fasting CKD patients with pre-existing cardiovascular disease which were predicted by an early rise of serum creatinine [6].

On the other hand, Kara et al.[7] have investigated 45 patients with stage 3 or higher CKD (mean age 66.8±10.3 years, 68.8% men) who chose to fast for 17.5 h and 49 (mean age: 64.1±12.6 years, 51% men) chose not to fast in Turkey at the 2015 summer. After multiple linear regression analysis, only advanced age was found to be associated with at least 25% drop in eGFR after Ramadan in the fasting group. They concluded that Ramadan fasting was not associated with increased risk of decline in renal functions in patients with stage 3–5 CKD. But, elderly patients may still be under a higher risk. This study is in line with Al Wakeel [3] study that included 39 CKD patients and 32 HD patients, the mean duration of sessions during Ramadan was significantly different from those before and after Ramadan (P=0.005). However, KT/V values did not differ significantly before, during, and at the end of Ramadan measurements (P=0.22). Of the HD group, eight (25%) patients had hyperkalemia on day 15 of fasting and five (15.6%) patients at the end of the month. Hyponatremia was documented in five (15.6%) HD patients on the 15th day of fasting and nine (28.1%) HD patients had hyponatremia on the 30th day of fasting. The final conclusion was 14 h fasting for 1 month was tolerated by CKD and HD patients, although there were considerable changes among HD patients in some of the blood chemistry variables without serious adverse events. Imtiaz et al.[8] studied 282 HD patients (252 patients who were not fasted vs. 34 fasted patients) with measuring body weight, blood pressure, serum potassium, serum albumin, and serum phosphorus at the beginning and during the last week of Ramadan. Their conclusion was dietary pattern changes and content during the Ramadan is safe in terms of electrolyte balance and blood pressure changes for patients on HD. It is also safe for those patients who want to fast during this month [8]. The previous study faced criticisms regarding the safety of Ramadan fasting in HD patients and the risk of fasting induce hyperkalemia due to intracellular potassium shifting, and also the risk of overload and fluid imbalance [9]. Regarding dialysis adherence, changes in biochemical and hemodynamics among HD patients during Ramadan, a prospective multicenter observational cross-sectional study that included 635 patients comparing fasting with a nonfasting stable adults revealed that there were no differences in the predialysis and postdialysis blood pressure; serum potassium, albumin or weight gain; diabetic status; and dialysis shifts time or days. Serum phosphorous was significantly higher in the fasting group. Fasters were significantly younger and more likely to be working, to miss dialysis sessions, and to have higher serum phosphorous levels [10]. The mortality rate among HD patients during Ramadan fasting was addressed in a large cohort (1841 patients) in a single center in Pakistan in the period between January 1989 and December 2012. The authors found that Ramadan reflected a higher frequency of death. Therefore, there is a need to evaluate the risk factors in a prospective study so that the dialysis patients can be better managed during this period [11]. Studies on the effect of Ramadan fasting on CKD and HD patients are still debatable with low levels of evidence. We consider conducting a randomized controlled trial to assess fasting in CKD (stage 3b–5) is unethical because the intervention may pose a certain risk and we advise all our patients who have an eGFR of less than 45 ml/min to avoid fasting in Ramadan. Patients who insisted on fasting are advised to have rest and avoid any exposure to dehydration, to check serum creatinine twice weekly during fasting, and to break fasting if there is an increase of serum creatinine of 0.3 mg/dl or higher.

Ramadan fasting effect on kidney transplants

Most of the studies suggested that Ramadan fasting is safe when the function of the renal graft is acceptable and stable for at least 1 year post-transplantation [12]. No study has reported any bad effects of Ramadan fasting for the transplanted kidneys; only one author reported adverse effects due to cyclosporine toxicity, acute rejection episodes, and urinary infections [13]. Hejaili et al.[14] have investigated the effect of Ramadan fasting on 43 RT recipients with stable renal function and compared their clinical and biochemical profile with 37 RT recipients who did not fast during Ramadan (2011 and 2012 summer; fasting duration of about 13 h in Riyadh, Saudi Arabia). The fasting group was divided into three subgroups, according to the degree of renal function at baseline, including low (<45 ml/min/1.73 m2), moderate (45–75 ml/min/1.73 m2), and high GFR (>75 ml/min/1.73 m2). No significant differences in the eGFR before and after 19.6±1.3 months were found in the fasting group, in the severe and moderate subgroups. However, a significant drop was noted in the high eGFR subgroup in both the fasting subgroup (96.4±15–84.9±20.7 ml/min/1.73 m2; P=0.17) and the nonfasting subgroup (92.9±15.8–82.3±18.2 ml/min/1.73 m2; P=0.019). The authors concluded that fasting in the month of Ramadan in 2 consecutive years, and during the hottest months, in Riyadh, Saudi Arabia, did not adversely affect kidney graft function. Many studies have previously assessed the Ramadan fasting effect on patients with RT, with normal or moderately impaired renal function, and they found no adverse effects [13],[15],[16],[17],[18],[19],[20]. The effect of Ramadan fasting on kidney transplant recipients during the first year of post-transplantaion is evaluated only in one small study which included 14 renal recipients who were transplanted between 1 and 7 months before Ramadan. The authors suggested that even during the first year of RT, the allograft kidney is able to tolerate the fluid restriction of Ramadan fasting. The main criticisms were the small sample size and the fasting was during winter season [21]. Argani et al.[18] have evaluated the immunologic changes in RT recipients during Ramadan fasting. Total white blood cell counts, serum C3, serum IgA level, serum IgM level, T cell count, and B-cell count were assessed. There was a statistically significant decrease in the B-cell count, serum IgM concentration, and serum C3 after Ramadan without any adverse effects of Ramadan fasting on renal allograft function. Also, the concentration of immunosuppressive drugs tends to remain stable during Ramadan with acceptable medications compliance during the fasting period [16]. If we look at all these publications critically, the evidence is not satisfactory and the risk is there. So, we advise all RT recipients to avoid fasting during the first year after transplantation or after any episode of allograft dysfunction. Also, we recommend against fasting in the presence of any comorbidity and in case of polypharmacy. Only, we allow stable recipients with perfect graft function whose immunosuppressive medication dosages and frequency are not interrupted by fasting provided that they are insisting to fast. Sometimes, it is easier for them to fast in the short days of winter rather than in summer.

Ramadan fasting effect on kidney stone disease patients

Renal colic, which is known as kidney stones, is a common disorder in the emergency departments and accounts for ∼0.6% of emergency departments visits [22]. Previous studies have shown that the incidence of renal stone disease changes seasonally [23]. Especially, the highest incidence rates have been reported during the warmer months such as July, August, and September [23],[24]. Thus, daily fasting period can last 15–16 h in summer. Fluid and diet restrictions during the month can influence the biochemical factors related to stone formation. Yet, studies on the effects of Ramadan fasting on the incidence of renal colic are scarce and have given variable and inconclusive results. Abdolreza et al.[25] have compared the number of patients admitted with renal colic between the four periods of (i) 2 weeks before Ramadan, (ii) the first 2 weeks of Ramadan, (iii) the second 2 weeks of Ramadan, and (iv) 2 weeks after the month of Ramadan (August 2008–October 2008).They concluded that the number of renal colic admissions was the highest in the first 2 weeks of Ramadan and there was an association between Ramadan fasting and the incidence of renal colic admissions.

In contrast, Cevik et al. [26], investigated 176 patients (n=89 in before Ramadan, n=87 in Ramadan) with renal colic. During Ramadan, 49 (73.1%) of 67 patients were admitted in the first half of the month and 20 (26.9%) patients were admitted in the second half of the month. Only urine density and white blood cell values in Ramadan and non-Ramadan period were significantly different (P=0.004 and 0.001). Also, hemoglobin, general crystal, and triple phosphate crystal values in the first and the second half of Ramadan were significantly different (P=0.04, 0.03, and 0.03). The final conclusion was that fasting in Ramadan does not change the number of renal colic visits. In addition, although fasting causes some changes in urinary metabolites, there is not enough evidence that these changes increase urinary calculus formation. Many studies have agreed with what reported by Cevik and colleagues [24],[27],[28]. In summary, there is still no strong evidence regarding if Ramadan fasting can induce renal stone formation in susceptible patients or not. Despite such controversies, nearly all studies are in agreement that consuming adequate amounts of water from dusk to dawn reduces the potential risk of dehydration in developing renal stones [12]. We advise patients with recurrent stone formers and passers with frequent episodes of renal colic to avoid fasting altogether.

Ramadan fasting effect on diabetic kidney disease patients

The prevalence of diabetes mellitus in several Muslim countries is high, and is increasing yearly at a rate of 10% as a result of urbanization and socioeconomic development [29]. Furthermore, Ramadan fasting poses a challenge to both physicians and patients. For fasting Muslims, the onset of Ramadan heralds a sudden shift in meal times and sleep patterns. This has important implications for physiology, with ensuing changes in the rhythm and magnitude of fluctuations in several homeostatic and endocrine processes. Sleeping patterns are often altered during Ramadan and several circadian rhythm changes have been noted, including changes in body temperature and cortisol levels [30],[31],[32],[33]. When fasting, insulin resistance/deficiency can lead to excessive glycogen breakdown and increased gluconeogenesis in patients with diabetes, as well as ketogenesis in patients with T1DM. As a result, the risks facing patients with diabetes, including hypoglycemia, hyperglycemia, diabetic ketoacidosis, dehydration and thrombosis, are heightened during Ramadan [34]. According to the last published guidelines by the International Diabetes Federation and Diabetes and Ramadan International Alliance, chronic dialysis or CKD stage 4 and5 and CKD stage 3 patients are considered very high risk and high-risk categories, respectively, and are exempted from fasting [35]. Despite exemptions existing for these patients, large number will insist on fasting, often against medical advice. In this situation, the patients should know the risks, receive structured education, be followed by a qualified diabetes team, check their blood glucose regularly, adjust medication dose as per recommendations, be prepared to break the fast in case of hypoglycemia or hyperglycemia, be prepared to stop the fast in case of frequent hypoglycemia or hyperglycemia or worsening of other related medical conditions. For more details one can revise reference [35].

Conclusion

There is a lack of strong evidence of research to guide the nephrologists because of low quality of observational studies that addressed this issue. As patients have permission not to fast after medical advice, we believe that nephrologists should be consistent in their advice that we have summarized in [Table 1].